Chemotherapy Options for Patients with Relapsed Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological malignancy in the industrialized world. Most patients present with advanced disease and, despite optimal surgical debulking and front-line chemotherapy with platinum- and taxane-based regimens, the majority will relapse. Relapsed EOC is incurable but there are various palliative treatment options. Patients who relapse more than 12 months after primary treatment have a good chance of response to re-challenge with platinum-based chemotherapy. Disease bulk, number of sites of disease, serous histology, type of chemotherapy, baseline hemoglobin, performance status, response to last chemotherapy, and presence of liver metastases also predict treatment outcome in relapsed disease. A number of new cytotoxic agents have become available over the last decade which are active in relapsed EOC. As single agents, altretamine, anthracyclines, etoposide, gemcitabine, oxaliplatin, taxanes, topotecan and vinorelbine all have response rates of about 20% in patients with relapsed EOC within 12 months of primary treatment. Response rates and perhaps disease-free survival can be increased with the use of combination chemotherapy but toxicity is also increased and, consequently, this approach needs further evaluation in randomized clinical trials. There are no data to support the use of high-dose or intraperitoneal chemotherapy in patients with relapsed EOC outside the context of clinical trials. Hormonal agents have been used in the treatment of patients with relapsed EOC for some time and, although objective responses are rare, disease stabilization may occur for a prolonged period in a small number of patients. Agents with novel mechanisms of action are emerging from the laboratory into clinical trials. Such agents may also stabilize relapsed disease and include gene therapies, signal transduction inhibitors, anti-angiogenic drugs, matrix metalloproteinase inhibitors and vaccines. None of these therapies, however, are at present part of the standard of care for ovarian cancer. The study of new agents in patients with relapsed EOC should, when possible, be in the context of randomized clinical trials in which patients are stratified according to known predictors of response to treatment. The issue of when to initiate treatment in women with relapsed disease is difficult as there is no proven benefit to treating patients who are asymptomatic with a rising CA-125 level but no evidence of bulky disease. Patients should not, however, be allowed to develop bulky or multiple sites of disease before treatment is started as the likelihood of response is reduced. Patients should at all times understand and be involved in treatment decisions.